Effects of Probiotics on Anxiety, Mood Balance, and Gastrointestinal Symptoms in Adults

EFFECTS OF A PROBIOTIC SUPPLEMENT ON ANXIETY AND MOOD BALANCE IN ADULTS

This document describes the study in detail. Please read the following information carefully before consenting to participate in this study and contact the researchers at probiotics.study@gmail.com if you have any questions.

Definitions of terms used in this information sheet:

Randomized: Participants are assigned to groups in a manner similar to drawing numbers from a hat.

Double-Blind: Neither the participants nor the researchers know who has been given the placebo or probiotic until the end of the study. Should it become necessary, that information can be obtained.

Parallel: Participants are divided into different arms (groups) of the trial that occur concurrently. For example, one half of the participants take the probiotic product and one half take a placebo.

1. Purpose

This research project will investigate the effects of probiotics on anxiety and mood balance, and associated psychological (e.g., memory issues) and physiological (e.g., digestive/gut health) factors. Another purpose is to determine whether probiotics influence cortisol levels; cortisol is a stress hormone that can be measured in saliva. We will also be looking at beliefs and traits that might be associated with placebo responding. The goal is to determine if probiotics might be useful in improving anxiety and mood balance, memory, and cortisol levels. This research is being conducted by Dr. Susan Potter, a clinical psychologist and associate professor in the Department of Psychology at Acadia University and Dr. Mark Johnston, a psychiatrist at True North Clinic in Kentville and Halifax. This research will also contribute to masters and honours theses at Acadia University.

2. Background

The gut is home to trillions of bacteria, both good and bad, which together form the gut microbiome. Good bacteria are referred to as probiotics. They play a role in normal human development, digestion, body weight, nutritional status, and immune system regulation, in addition to influencing brain functioning. Environmental factors, including antibiotics, cesarean birth, illness, stress, and diet can disrupt the balance of bacteria in the microbiome, which may in turn contribute to a variety of health problems, both mental and physical. For example, there is a strong link between gastrointestinal disturbances and anxiety, which in turn is associated with disturbances of the gut microbiome. Probiotics have been shown to help relieve gastrointestinal problems and early studies suggest they may also be helpful in improving symptoms of anxiety and negative mood. In mice, probiotics have even been shown to improve memory.

3. General Overview of the Study

Participants will be involved in the study for a six-week period: a one-week information collection period and five weeks in which they take probiotics or placebo. All participants will meet with the researcher twice and complete a set of questionnaires and some memory tests each time. They will also provide two saliva samples that will be analyzed for cortisol, a stress hormone associated with anxiety and mood balance that may be influenced by probiotics.

Throughout the study period, all participants will be asked to complete a weekly checklist of gastrointestinal and anxiety/mood balance symptoms.

4. What is a placebo?

A placebo is an inert substance (sometimes called a “sugar pill”) that would not be expected to have any health effects. A “placebo effect” is an improvement in health, or sometimes the experience of side-effects, that cannot be attributed to a treatment (i.e., it occurs in response to something that could not produce that result itself, a placebo). Placebo effects often occur when a person believes they are taking an active treatment and, as a result, expects or anticipates that it will have an effect. Therefore, it is important to have a “placebo control” group in a study like this because if people’s symptoms get better because of their expectations, we wouldn’t know if the probiotics actually worked. In this study, we will also be examining factors that might influence placebo responding such as people’s beliefs about their symptoms and some personality traits.

5. Who can participate?

In order to participate in this study you must meet certain requirements. For example, you must be at least 18 years of age, live in the Wolfville or Halifax area, experience some symptoms of anxiety, and check your email regularly. To find out if you are eligible to participate, please visit the study website, http://probioticstudy.com and look over the eligibility requirements (after reading the information about the study, click on the “eligibility” tab at the top of the page). If all the statements apply to you, you will be asked to read an online consent form and click a link to complete a short online questionnaire asking about your health, medical history, foods you consume, and anxiety and mood balance. If you are a good candidate for the study and you are willing to participate, you will be contacted by one of the researchers within the following week.

6. What will I be asked to do?

Prior to meeting with the researcher, there will be a one-week information-gathering period. During this time, you will be asked to keep a food diary to keep track of what you eat each day. The amounts need not be exact but it is important to list all foods and drinks consumed. This should take 5 to 10 minutes to complete. You will also answer a few questions each evening about your mood and gut/bowel health. This will be explained to you over the phone or via email when the researcher contacts you. After this one-week period, you will not have to complete the food diary again, but you will continue to answer the questions about mood and gut/bowel health once a week during the study period.

A. Initial Appointment

You will be asked to come to our Acadia or Halifax office to meet with one of the researchers. This appointment will be approximately one hour long. During this session, the following things will happen:

The study requirements will be explained to you in detail and, if you agree to participate, you will be asked to sign an informed consent form.

You will talk with the researcher about your anxiety, mood balance, other mental health issues and any physical health problems you may have, and complete some questionnaires asking about these types of issues.

You will be given some brief memory tests that will assess your short-term and long-term memory for both verbal (auditory) and visual material. For example, you will be asked to try to remember a list of words and some geometric designs.

You will be given two saliva collection kits to take home. These consist of a small test-tube and a straw that you put in your mouth and drool or spit into. Instructions on when and how to take the saliva samples are provided below. We will analyze the saliva samples for cortisol, a stress hormone, to see if probiotics have any effect on cortisol levels.

You will be given a five-week supply of either probiotics or placebo to begin taking after you collect your first morning saliva sample. Neither you nor the researcher will know whether you are getting probiotics or placebo – the packages all look alike. The probiotic packets will contain a flavoured probiotic powder (Probio’Stick) that contains three billion live bacteria (or “culture forming units” - CFUs), produced by Lallemand Health Solutions. These probiotics are microencapsulated to protect them from stomach acids as they travel to the intestines and colon where they are believed to exert their beneficial effects. The placebo packets contain a flavoured powder that is physiologically inert (i.e., it will not have any effect on your symptoms) that looks and tastes just like the Probio’Stick.

B. Weekly Questionnaires and Saliva Sample Collection

Once a week throughout the study, you will complete a gastrointestinal and anxiety/mood balance symptom checklist asking about the severity of any symptoms you experienced during the previous week. This should take about five minutes.

You will collect your first saliva sample the morning after your first meeting with the researcher. Instructions for saliva sample collection are as follows:

First sample: Within the first few days (preferably the morning after your appointment), you should collect your first baseline saliva sample. Do this first thing in the morning right after you wake up. Do not eat or drink anything until after you have collected your saliva sample. Write the date and time on the test-tube label. Follow the instructions with the kit provided. If your mouth is too dry, try to imagine biting into a lemon or eating your favourite food. After collecting the sample, immediately place it in your freezer (deep freezer if you have one).

Second sample: One day before your second meeting with the researcher, you will collect another saliva sample. Write the date and time on the test-tube label. Place the sample in your freezer right away. Bring both saliva samples to your meeting.

C. Five-week Probiotic or Placebo Phase

You will consume one packet of probiotic or placebo (whichever you were given) each day for five weeks. Most people like the taste of the powder. Open one of the packets of powder, tilt your head back, and dissolve it on your tongue. Try to take it at approximately the same time each day, preferably first thing in the morning or at night before bed. It is best to take it with some food or milk.

You will complete the symptom severity checklist at the end of each week.

You will receive emails from the researchers every few days during the first week to check in and see how you are doing. Please email us back if you have any questions.

Part way through this five-week period, you will be contacted by the researchers to set up your next appointment, which will take place near the end of the fifth week.

Towards the end of your fifth week of taking the probiotics or placebo, you will collect another morning saliva sample, as before. Write the date and time on the label. After collecting the sample, immediately place it in your freezer. Bring your saliva samples with you to your next meeting with the researcher.

D. Second Appointment

Your second appointment with the researchers will take place when you are within a few days of finishing your supply of probiotics or placebo. Please remember to bring your frozen saliva samples with you. This meeting should last about 45 minutes, during which:

You will complete some of the questionnaires again that you completed at the beginning asking about anxiety and mood balance and your physical health.

You will be given some memory tests similar to those you had during the first meeting.

Have any questions answered

Receive $50 for your participation

7. What are the ingredients of the probiotic and placebo powder and will I feel any beneficial or adverse effects from taking them?

The probiotic powder is made up of the following ingredients: two strains of probiotics, Lactobacillus helveticus and Bifidobacterium longum subsp. longum (3*109 CFU per sachet), artificial fruit flavour, xylitol (sweetening agent), matodextrin (filler), and malic acid (acidifying agent). The placebo powder has the same ingredients minus the probiotics.

If you are taking the probiotic powder and it is working, you may notice an improvement in your mood, anxiety levels, and any digestive issues you may have had.

If you are taking the placebo powder, there will be no change in your symptoms as a result of consuming the powder. However, some people taking the placebo will experience a “placebo effect” and feel an improvement in their symptoms (or sometimes negative side-effects) that they will attribute to the powder and may guess incorrectly that they are taking the probiotic.

8. What are the risks and advantages of participating?

There are no known risks associated with participating in this study. The probiotics have been studied before, are available over-the-counter in pharmacies and are generally considered safe. It is possible that there are risks of which we are not aware at this time. If we become aware of other risks, we will notify all research participants immediately. If you become ill during the study period, please contact the researchers as soon as possible. If you are seriously ill, please contact your physician and/or go to your nearest emergency department.

There will be no direct benefits to you from participating in this study (other than a small financial compensation) because we do not know for certain that probiotics will help with anxiety and mood balance, although the results of other past research are promising. However, you will be contributing to the advancement of science and furthering our knowledge about the potential therapeutic effects of probiotics on anxiety and mood balance.

9. Can I participate if I am taking other medications?

Please discuss this with your physician before enrolling in this study and please notify the researchers of any medications you are taking. For the purposes of the research, it is okay if you are taking medications for depression and anxiety as long as you have been taking a stable dose for at least two months and the dose is unlikely to change during the study period. However, you cannot participate if you are taking antibiotics, undergoing chemotherapy, or if you are taking medications for HIV. There may be other medications that are also contraindicated, so please discuss this with the researchers.

10. Are there other treatment options for anxiety?

Yes. There are a lot of different medication options. You may want to discuss these with your physician. There are also some forms of psychotherapy (e.g., Cognitive-Behavioural Therapy) that have been shown to be effective for the treatment of anxiety and mood balance.

11. Will I be paid or receive bonus points towards my Introductory Psychology or Research Methods course for participating in this study?

You will be paid $50 for your participation. In order to receive your $50, you must complete all of the study requirements (complete questionnaires as requested, collect the requested saliva samples, take your probiotic or placebo powder each day, etc).

If you complete the study requirements, you will receive $50 at your final meeting with the researcher.

Students enrolled in PSYC1013/1023 and 2013/2023 at Acadia University, who complete the study before final marks are submitted, may receive a combination of bonus points toward their final grade and money for participating as follows:

3 bonus points for completing the one-week information collection period

$50 for completing the study

• Students must complete all parts of the study in order to receive monetary compensation.

12. Can I withdraw from the study if I change my mind?

You may withdraw from the study at any time for any reason. However, you will not receive any financial compensation. You may also withdraw your data, but you must notify the researchers within one week of completing or withdrawing from the study.

13. Can the researcher withdraw me from the study?

You may be withdrawn from the study without your consent for not following instructions or failing to complete the required tasks; e.g., not completing the questionnaires, not taking the probiotics, missing appointments with the researcher, etc. If you are withdrawn by the researcher for not completing the required tasks, you will not receive compensation.

14. Will the information I provide be kept confidential?

Yes. Once you have completed the online eligibility questionnaire and the researcher has contacted you, your name and contact information will be removed from the server and you will be assigned a code number. From that point on, all your questionnaires and other data will be identified by code number only – your name will not appear on anything except the master code list and this will be stored in an encrypted, password-protected file on a password-protected computer. When saliva samples are sent for analysis, they will be identified by code number only. All online questionnaires will be housed on Canadian servers. When the results of this study are presented at professional conferences, discussed in student theses, and published in scholarly journals, only group results will be discussed and individual participants will not be identified. All data storage drives, paper data, and saliva samples will be stored securely in a locked office at Acadia University.

15. Who is funding this study and are there any conflicts of interest?

Funding for this study comes from two different sources:

Lallemand Health Solutions in Montreal, QC

Acadia University faculty research grant (Article 25.55)

Lallemand Health Solutions is providing the probiotics, the placebo, and financial support, and they stand to benefit from the results should the study reveal any therapeutic effects of their encapsulated probiotics. However, the company is at arm’s length and is not involved in data collection or analysis. This research may provide scientific evidence that their probiotic product has therapeutic potential, but they are equally open to the possibility that the results might not be in their favour.

16. By participating in this study, will I receive free psychotherapy for my anxiety and/or negative mood?

Unfortunately, we are not able to provide our study participants with psychotherapy. However, we would be happy to refer you to a mental health professional if you feel you need to see someone. We recognize that by completing questionnaires focusing on anxiety, mood, and physical ailments, you may feel upset as you reflect on these issues; if this should happen and you find yourself in need of counseling, please contact one of the following:

If you have a therapist, please contact him or her.

The Mental Health Clinic at

Valley Regional Hospital, Kentville (902-679-2870)

Hants Community Hospital, Windsor (902-792-2042)

Queen Elizabeth II Hospital, Halifax (902-473-2043)

If you would like a specific referral, please contact us.

If you are in need of urgent help, please visit your nearest hospital emergency department.

17. Who do I talk to if I have ethical concerns about the research or questions about the study?

If you have any ethical concerns about this study, please contact the Acadia University Research Ethics Board chair, Dr. Stephen Maitzen (smaitzen@acadiau.ca or 902-585-1498). If you have specific questions about this study, please contact the researchers named at the top of this document.

You will be given a copy of this information sheet to refer to if you participate in this study.

This clinical trial has been approved by the Acadia University Research Ethics Board and Health Canada.